Jaundice, General
also see Anemia, hemolytic dz of nbn

Quick Reference

Intensive discussion of Bilirubin metabolism, Presentation by age Jaundice, Physiologic/Breast Milk Phototherapy, Hyperbilirubinemia graphs, Jaundice on physical exam, Anemia, hemolytic dz of nbn, Phototherapy, Differential for Uncong hyperbili, Bilirubin encephalopathy and Kernicterus, Differential for Cong Hyperbili Evaluation of Neonatal Cholestatis, Management of Chronic Cholestasis.

If admitting an infant to the hospital for phototherapy or possible exchange transfusion, directly admit and bypass the ER (they tend to investigate sepsis and delay what is REALLY needed: phototherapy).

Approximate/suggested guidelines for initiation of phototherapy. Based on risk factors, TSB level, and age. The following data points are extrapolated from the graphs in the July 2004 AAP clinical guidelines. See chart for easier interpretation and plotting:  Hyperbilirubinemia graphs

If pt is >38wk and well, then low risk & higher thresholds for therapy:

If patient is >38wk + risk factors or 35-37 6/7wk and well, then medium risk & lower thresholds for therapy

If patient is 35-37 6/7wk + risk factors, then high risk & lowest threshold for therapy:

Other Numbers/Scenarios to know:

• A 1986 study in Pediatrics by Maisels showed that 95% of infants admitted to the newborn nursery (?at how many hours?) had a TSB concentration of 12.9 mg/dL or lower, so this has become the accepted upper limit of physiologic jaundice in the newborn nursery, where all infants with a serum bilirubin level >13 mg/dl require a minimum work up.
• More recent studies show by 96 hours (DOL 5+), TSB levels of 17 represent the 95th percentile, indicating an increased incidence of jaundice (probably due to increased numbers of women feeding at discharge)
• It is common to see a 3 week old, breastfed, jaundiced infant (some healthy breastfed infants may have indirect hyperbili as long as 3 mos) HOWEVER, any infant still jaundiced at 3 weeks of age must have a fractionated bili checked to r/o cholestatic d/o.
• Know what is normal: Physiologic/Breast Milk Jaundice
• Risk zone based stratification: % of patients who go on to develop TSB >= 95%ile (study by Bhutani et al.)
  • low risk: 0
  • intermediate, low (40%ile TSB): 2.26%
  • intermediate, high (75%ile): 12.9%
  • high (<95%ile): 39.5%
• Extreme hyperbilirubinemia (>30) is rare: 1/10,000 infants
• know the risk factors that increase or decrease risk of severe hyperbilirubinemia

AAP Practice Guidelines regarding the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation (combined with info from other sources)

1. When to do infant cord blood Coombs and Type & Screen:
   • if a mother has not had prenatal blood typing
   • if a mother is Rh-negative
   • If mother is O+, there is no potential for hemolysis due to ABO or Rh incompatibilty and therefore it is an option to test the cord blood. (Note: there may be other minor blood group antigen mismatches that could cause hemolytic disease)
2. Clinically assess for jaundice every 8 to 12 hours: Jaundice on physical exam
3. When to test TSB or TcB (transcutaneous bilirubin)
   • on every infant who is jaundiced in the first 24 hours after birth
   • if the jaundice appears excessive for the infant’s age
   • if there is any doubt about the degree of jaundice
   • Interpret all bili levels in terms of hours, not days
   • Refer to Hyperbilirubinemia graphs.
   • Note: although the indirect fraction is the toxic fraction, the AAP recommends using the TSB to determine the need for exchange transfusion.
4. When to be concerned about a pathologic process, and further workup indicated
   • know the risk factors that increase or decrease risk of severe hyperbilirubinemia
   • t bili rising greater than 5 mg/dL/day or 0.2 mg/dl/hour
   • t bili > 12 in term infant, 10-14 in preemies
   • persistent jaundice after 10-14 days
   • direct bili > 2 (High direct hyperbilirubinemia? Aside from usual ddx, may also be caused by intrauterine transfusion.) Differential for Cong Hyperbili.
   • 75%ile for TSB levels (low intermediate risk). Consider workup if beyond these levels (ie. type and coombs, CBC, consider G6PD, esp in black infant.
     1. DOL 1 (<24 hours): 6
     2. DOL 2: 6-11
     3. DOL 3: 11-13
     4. DOL 4: 13-15
     5. DOL 5: 15-16. Peaks here in breast feeding jaundice. In preemies and breast fed infants, peak is relatively higher and lasts longer
     6. by DOL14: normal bili, CB <20%
     7. Example: Jaundice in a severely bruised infants needs no further explanation, a 4-5 day old breast fed infant with TSB is 16 doesn't need further workup, but does require monitoring to ensure that the bilirubin level does not becomes excessive. When doing a serum TSB, also use your hand-held machine to correlate and simplify future measurements.
5. When do to urinalysis and urine culture
   • if elevated direct/conjugated bilirubin level (evaluate for sepsis if indicated)
   • if patient is a readmission, consider also Urinary reducing substances to r/o d/o of carbohydrate metabolism
6. Consider the differential diagnosis: Presentation by age, Anemia, hemolytic dz of nbn, Differential for Uncong hyperbili, Differential for Cong Hyperbili, Evaluation of Neonatal Cholestatis, Management of Chronic Cholestasis
7. Start Phototherapy if indicated. Monitoring while on intensive phototherapy: IF TSB is
   • 25 or more, rpt TSB in 2-3 hrs
   • 20-24, rpt in 3-4 hrs
   • 19 or less, rpt in 4-6 hrs
   • if TSB continues to fall, rpt in 8-12 hrs
8. Breastfeeding tips
   1. Prevention: encourage frequent breast feeding 8-12x/day; do not supplement with water or dextrose water
   2. Treatment: increase frequency of nursing, continue nursing but start phototherapy (this option is fine as long as TSB <25 OR temporarily stop breast feeding and for 48 hours and substitute formula (do this if TSB 25 or more). If using PT, monitor for inadequate intake, dehydration or excessive weight loss, and supplement with expressed breast milk/formula as necessary.
9. When to do... (if checking these labs, recheck TSB in 4 to 24 hours dep on pt condition
   1. Type and Direct Coombs (Direct antiglobulin, DAT, identifies Ab attached to RBC), CBC/smear/retic count, direct bilirubin, G6PD level
   • For infants receiving phototherapy
   • TSB rising rapidly, crossing percentiles and unexplained by history and examination
   • TSB >75%ile (low intermediate risk of developing hyperbilirubinemia)
   • If TSB level is approaching exchange levels or not responding to phototherapy, do the above and send albumin. Administration of gamma globulin in isoimmune hemolytic disease is recommended if TSB is rising despite phototherapy or if level is within 2-3mg/dl of the exchange level. Albumin level of less than 3 is one risk factor for lowering the threshold for phototherapy use.
   • Remember that a normal G6PD level in a hemolyzing neonate does not rule-out deficiency.
   • Have a low threshold of obtaining G6PD level in a black, jaundiced neonate. Black infants as a whole have a much lower TSB level than white infants, so significant jaundice should raise the suspicion of G6PD deficiency.
10. Liver Enzymes, Labs
11. When to consider exchange transfusion when patient is on intensive phototherapy. Check albumin.
    1. TSB not falling
    2. TSB moving closer to level for exchange transfusion
    3. If TSB/Albumin ratio (mg/dL  / g/dL)
       1. 8.0 if GA 38 0/7 and well, or
       2. 7.2 if GA 38 0/7 and higher risk*, or isoimmune hemolytic disease, or G6PD deficiency.
       3. 7.2 if GA 35 0/7 - 37 6/7 and well,
       4. 6.8 if GA 35 0/7 - 37 6/7 and higher risk*, or isoimmune disease, or G6PD deficiency
       5. * isoimmune hemolytic disease, G6PD deficiency, asphyxia, significant lethargy, temperature instability, acidosis, sepsis, albumin < 3.0.
12. For discussion of 'rebound' and outpatient followup see Phototherapy.
13. Regardless of jaundice, in a all newborns, the AAP has repeatedly recommended f/u within 48 hours if a patient has been discharge at less than 48 hours of age, a recommendation that is widely ignored. BUT the recommendation has become stricter, and 2 day f/u is necessary if the infant has spent less than 72 hours in the hospital
14. Tell mom to breast feed frequently, 8-12x per day, the more the better. Monitor for normal Bowel movements and expected weight loss.
15. The negative predictive value of a predischarge TSB or TcB below the 40th percentile—or below the 50th percentile, according to some studies—is high. A newborn with a TSB level below the 40th or 50th percentile is at very low risk of severe hyperbilirubinemia.
16. If predischarge TSB is 75%ile or higher
17. What we're trying to avoid: Bilirubin encephalopathy and Kernicterus
18. If jaundice is present at or beyond three weeks of age, or infant is sick
    • measure a total and direct bilirubin
    • check results of the newborn screen (esp galactosemia, hypothyroid)
    • evaluate for cholestasis if direct hyperbilirubinemia present

Wave of the future

• tin-mesoporphyrin is a promising drug that inhibits heme oxygenase, the enzyme in the first step of heme to bilirubin conversion

References

Contemporary Pediatrics. May and June 2005

CLINICAL PRACTICE GUIDELINE: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. PEDIATRICS Vol. 114 No. 1 July 2004, pp. 297-316